Equine gastric ulcers can affect horses at any age. Up to 88 percent of racehorses and 59 percent of non-race horses are affected by equine gastric ulcers. Even foals and non-performance horses are not immune under some environmental and management conditions.
The stomach of the horse is made up of two distinct areas. The bottom is glandular and has an effective protective coating to protect it from the acid produced in that area. The upper portion functions as a mixer of the stomach contents and is not afforded the extensive acid protection mechanisms. It is most prone to ulcer development when exposed to more acidic conditions.
Horses evolved as grazing animals that were engaged in nearly continuous feeding activity. Therefore, a horse's stomach produces acid continuously and not only in response to stimulus from feeding. With extended time periods between feedings for stalled horses, the gastric pH may fall rapidly, contributing to the development of equine gastric ulcer syndrome (EGUS). Withholding feed for several hours from horses may depress gastric fluid pH to 2.0 or less.
EGUS may express itself both as a symptomatic and asymptomatic disease. The majority of horses with ulcers do not show outward symptoms. However, they may exhibit more subtle symptoms such as poor appetite, decreased athletic performance, weight loss, and a dull or rough hair coat. Horses with more severe cases of EGUS will show signs of abdominal pain (colic) and/or bruxism (grinding the teeth).
EGUS is often a man-made disease. Not only have feeding times often been reduced to twice daily, but the animals are fed higher nutrient-dense diets, leaving the horse with long periods of idle time between meals. Grain-rich diets contribute to increased volatile fatty acid production during the digestion process in the stomach, further contributing to EGUS.
The incidence of gastric ulcers can also be influenced by stress (environmental, dietary, and physical). The onset of race training, hauling, showing, or weaning may induce ulcer formation in as few as five to seven days.
Strenuous exercise is another contributing factor to EGUS. Activity that involves a tightening of the abdominal muscles causes an increase in intra-abdominal pressure. This increase in pressure forces a portion of the hydrochloric acid and bile acid normally found in the lower glandular region of the stomach upward into the squamous or non-glandular region of the stomach. This ultimately leads to gastritis and ulcer formation in the non-glandular region.
Additionally, the repetitive use of non-steroidal anti-inflammatory drugs (NSAIDs) such as phenylbutazone, flunixin meglumine, or ketoprofen may decrease the production of the protective mucus layer that provides the stomach a safety barrier from the gastric acid. This diminished protection increases susceptibility to ulcer formation.
The most recognized treatment for EGUS is Gastrogard® veterinary preparation. The active ingredient is omeprazole (marketed for humans as Prilosec® pharmaceutical preparation). Gastrogard® veterinary preparation is the only FDA-approved treatment for equine stomach ulcers. Because of the high rate of ulcer recurrence, either modified animal management strategies or ulcer prevention strategies must be employed. More recently, Ulcergard® veterinary preparation was introduced by Merial, Ltd. of Duluth, Ga., as a non-prescription, FDA-approved medication for prevention of gastric ulcers in horses. When horses previously administered Gastrogard did not achieve a cured status in ulcer score, subsequent Ulcergard® treatment produced highly variable and sometimes negative results. A 30-day treatment regimen of Gastrogard® veterinary preparation can cost between $1120 and $1680, depending upon dosage and individual veterinarian pricing, while the Ulcergard® veterinary preparation prevention programs cost between $300 and $360 per 28-day prevention program for horses between 600 and 1200 pounds of body weight.
Omeprazole is a proton pump inhibitor (PPI) that inhibits gastrointestinal acid secretion. Omeprazole is absorbed in the small intestine. A pharmaceutical oral solid dosage form of omeprazole must be protected from gastrointestinal acid so that it can pass to the small intestine. An enteric coating is often used to protect the active ingredient from degradation by stomach acid to maintain pharmaceutical activity.
Due to these high costs, many horse owners have sought out and purchased compounded variations of omeprazole paste or suspension products from their veterinarian. These are less expensive, costing approximately $200 to $240 per month for a preventative program. Unfortunately, these compounded formulations often lack efficacy. The efficacy and potency of omeprazole is difficult to maintain through the compounding process. Two recent studies have revealed that compounded omeprazole suspensions were ineffective in healing gastric ulcers in race horses.
Since ulcer recurrence is very problematic, horse owners have sought less expensive prevention programs that include the feeding of antacid-type additives to potentially protect their animals. These products include a wide variety of buffering and/or neutralizing compounds and/or mineral ingredients. These products have very mixed reviews, with little (if any) published scientific data to support inferences that the products prevent ulcer development or facilitate healing of gastric ulcers.
Other potential problems may limit the suitability of ingredients for use in antacid-type feed supplements:
A. Low capacity to neutralize meaningful amounts of gastric acid.
B. Reactivity rate is not proportional to retention time in the stomach.
C. Ability to be retained in the stomach beyond the gastric fluid turnover rate.
D. Palatability and general acceptability to oral and esophageal tissues.
Hydrochloric acid and volatile fatty acids contained in gastric fluids are strong acids. Weak bases, such as calcium carbonate, dicalcium phosphate, or magnesium oxide, cannot be fed in sufficient amounts to practically neutralize the excess acidity in the stomach environment and reduce the incidence of gastric ulcers. Additionally, the weak bases have limited solubility in water and their acid neutralizing capability is only moderate. They may be somewhat more effective in providing a degree of neutralizing capacity by the time they reach the lower tract than they are in the upper tract.
An effective neutralizing agent must possess the ability to be reactive in a time period that is proportional to the time it is present in the stomach. Horses exhibit a rapid turnover rate in stomach contents with liquid retention times as low as 15 to 60 minutes. Therefore, solubility and reactivity in a low pH environment at body temperature is critical.
If a horse consumes an antacid product at feeding time or is dosed with a suspension or paste product at another time, this ingredient can only be effective while it is present in the stomach. Most water-soluble buffer ingredients have a very short retention time (usually <60 minutes) in the stomach, leaving the horse relatively unprotected in only a short time after administration. Many of these weak base products would require 6-12 doses distributed through the day in order to be effective in providing protection from excessive gastric acidity.
Stronger bases such as sodium hydroxide, magnesium hydroxide, and calcium hydroxide are available and possess the capability to neutralize the strong acid effects in the stomach. However, they are generally highly unpalatable to the horse and can be damaging to tissues in the mouth and esophagus. If diluted to such an extent as to be palatable and tissue-friendly, their effectiveness is doubtful unless dosed in very large amounts at very frequent intervals.
Another complication for horse owners attempting to find non-prescription solutions to alleviate excess acidity in the stomach of their horses is the unexpected side effects of some of the ingredients found in particular equine antacid products.
U.S. Patent Application Publication No. 2005/0163867 discloses a composition for treating ulcers in mammals. The composition contains magnesium hydroxide (a strong base) as a primary active neutralizing ingredient. U.S. Pat. No. 6,284,265 discloses an equine antacid product, while specifically noting that magnesium hydroxide can produce an ataxic effect in horses at higher dosage rates.
There are also products that include aluminum compounds such as aluminum phosphate, aluminum hydroxide, and/or dihydroxy-aluminum-sodium-carbonate. The side effects for this group of compounds include reduced crude protein digestibility, increased urinary excretion of iron, reduced absorption of ferrous sulfate (a common source of iron in equine feeds), reduced phosphorus digestibility, and reduced gastrointestinal absorption of amino acids (building blocks of protein for the body).
There are also important negative ingredients/drug interactions from this group of aluminum compounds, including reduced gastrointestinal absorption of chlortetracycline, oxytetracycline, and tetracycline (important antibiotics in treating respiratory infections) and reduced bioavailability of prednisone (an important corticosteroid used in the treatment of severe allergies, skin disease, and arthritis). Additionally, in the case where ascorbic acid (vitamin C) has been included in the diet (contained in many commercial athletic and senior horse feeds), the ascorbic acid/aluminum phosphate interaction poses a high risk of excessive absorption of aluminum.
Therefore, there is a need for an effective lower cost composition and method for improving the gastrointestinal health in horses by reducing gastric ulcers. The composition should avoid negative interactions and side effects, while providing a straight forward delivery method.